An intrathoracic giant tumour and vanishing lung cyst after tumour resection.

A 65-year-old woman was brought to the emergency unit with an approximately 6-month history of persistent fever and cough. Chest computed tomography (CT) demonstrated a 16-cm heterogeneous mass with adjacent large cyst (approximately 4.0 cm). The patient underwent CT-guided biopsy, and benign solitary fibrous tumour (SFT) was immunohistochemically diagnosed. As the symptoms were thought to be due to enlargement of the tumour, surgery was deemed necessary, and the tumour was successfully resected. Based on morphological and immunohistochemical examination of the resected specimen, the final diagnosis was dedifferentiated SFT (DSFT). Follow-up CT verified disappearance of the pulmonary cyst. The cyst was speculated to be caused by a check valve mechanism, which may also suggest a rapid growth of the tumour. At the time of writing, 2 years post-operatively, no tumour recurrence has been identified. This represents the first report of intrathoracic giant DSFT with a cystic lesion returning to normal lung parenchyma.

Pleurography (thoracography) for pleural fistulas: A case series.

BACKGROUND: Pleurography (PG) has been described previously but has not gained popularity. PG can determine the exact air leak points in the lung, which is important for treating pneumothorax and pleural fistulas. We believe that the usefulness of PG should be reassessed, and here we describe the method, air leak detection rate, and common complications. METHODS: From the 1210 cases of pleural fistulas that were treated at our institution between March 2015 and October 2018, 275 patients with recurrent primary pneumothorax or secondary spontaneous pneumothorax were selected for this study. PG was performed in 127 patients with persistent air leakage during exhalation. In addition, 35 patients with postoperative complications of air leakage persisting for 7 days or longer were included. RESULTS: Air leak points were detected in 119 patients (73%), in the apex of the lung in 65 cases, in the basal segment in 13 cases, and in the middle lobe or lingular segment in 9 cases. There were 8 cases of hilar lesions, 12 cases of S6 lesions, 8 cases of upper lobe lesions other than apex, and 4 cases of upper mediastinal lesions. Complications within 30 days were observed in 10 cases (6.2%), with 8 grade 2 cases involving fever, 1 grade 3 case involving infection, and one grade 1 case with abdominal distension. CONCLUSIONS: The incidence of grade ≥3 adverse events after PG was 0.6%, which is considered acceptable. Our findings suggest that PG is a safe examination method to identify air leaks before surgery for pleural fistulas.

COVID-19 pneumonia and an indelible ground-glass nodule.

When a chest computed tomography (CT) scan is performed in the diagnosis and treatment of coronavirus disease 2019 (COVID-19) pneumonia, the possibility of lung neoplasm should be kept in mind if the ground-glass nodule (GGN) shows features that are non-specific for viral infection, such as solitary nature, relative roundness, well-defined borders, and distance from the pleura.

Ingenuity of minimally invasive thoracoscopic lobectomy for undiagnosed pulmonary tumour.

A 51-year-old man was referred to our hospital, with a dumbbell-shaped nodule measuring 40 mm in the right upper lobe of the lung. He was a current smoker with diabetes mellitus and bronchial asthma. The transbronchial biopsy was performed. However, definitive diagnosis was not obtained from the excised specimens. Bacterial culture of bronchial lavage fluid also yielded negative results, including for tuberculosis. After eight months of observation, the tumour had slightly increased in size. Surgery was planned to resect the tumour for definitive diagnosis. Because of the size of the tumour, a lobectomy of the lung was scheduled with the patient's consent. Four small incisions, each less than 1.2 cm long, were made in the chest wall for thoracoscopic surgery. To remove the specimen, we made a 3-cm longitudinal incision 1 cm below the xiphisternal joint. The patient complained of no chest pain after surgery. The post-operative course was uneventful.

Modified marionette technique for uniportal video-assisted thoracic surgery: a case report.

BACKGROUND: The current state of thoracoscopic technology allows less invasive surgical procedures and requires fewer ports and incisions. Totally video-assisted thoracic surgery with a single port has emerged as the least invasive thoracoscopic approach. However, uniportal video-assisted thoracic surgery brings about considerable difficulties, necessitating the development of skillful techniques as well as specific surgical devices. In such situations as dense pleural adhesion and anatomical abnormality, it may be more burdensome, necessitating the conversion to conventional multiportal video-assisted thoracic surgery or even to thoracotomy. To troubleshoot these situations, we herein propose the use of additional technique which could support to sustain the confident operative field for uniportal video-assisted thoracic surgery. This procedure also provides the same cosmetic outcomes as uniportal video-assisted thoracic surgery. CASE PRESENTATION: A previously healthy, 77-year-old female was referred to our hospital, with a lung adenocarcinoma measuring 28 mm in the right upper lobe. Uniportal video-assisted thoracoscopic surgery was planned to resect the tumor. During operation, we found the incomplete interlobar fissure between the upper and the middle lobe and the abnormal lobulation of the upper lobe. Therefore, the modified marionette technique was introduced to make the procedure safer and easier. This technique proposed herein consists of employing the untethered gripping forceps to retract the lung, not requiring additional traumatic trocars. The postoperative course was uneventful and the patient `was discharged in 1 week after a modified uniportal video-assisted thoracic surgery for the right upper lobectomy. CONCLUSIONS: The modified marionette technique produced sufficient operative views to attain uniportal video-assisted thoracic surgery safely in this case, rendering operative conversion unnecessary.

A novel dual-covering method in video-assisted thoracic surgery for pediatric primary spontaneous pneumothorax.

BACKGROUND: Primary spontaneous pneumothorax (PSP) generally occurs in young adults, whereas pediatric PSP is uncommon. It is difficult to source reliable data on pediatric PSP, the management of which is based on guidelines for adult PSP; however, the rate of recurrence after video-assisted thoracoscopic surgery (VATS) for pediatric PSP is reported to be higher. METHODS: We reviewed retrospectively a collective total of 66 surgical cases of a first pneumothorax episode in 46 children under 16 years of age, who were treated at our hospital between February, 2005 and November, 2017. RESULTS: The surgical cases were divided into two groups, depending on how the treated lesions were covered. In the dual-covering (DC) group, the PSP was covered by oxidized regenerated cellulose and polyglycolic acid (8 patients; 13 cases) and in the single-covering (SC) group, the PSP was covered by oxidized regenerated cellulose (38 patients; 53 cases). There was no incidence of recurrence after surgery in the DC group, but 17 cases (32.1%) of recurrence after surgery in the SC group. This difference was significant. CONCLUSION: The DC method prevented the recurrence of PSP more effectively than the SC method after VATS in pediatric patients. Long-term follow-up after VATS for pediatric PSP is also important because of the risk of delayed recurrence.

A total pleural covering of absorbable cellulose mesh prevents pneumothorax recurrence in patients with Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is a recently recognized inherited multiple cystic lung disease causing recurrent pneumothoraces. Similarly to the lesions in patients with lymphangioleiomyomatosis (LAM), the pulmonary cysts are innumerable and widely dispersed and cannot all be removed. We recently described a total pleural covering (TPC) that covers the entire visceral pleura with oxidized regenerated cellulose (ORC) mesh. TPC successfully prevented the recurrence of pneumothorax in LAM patients. The purpose of this study was to evaluate the effect of an ORC pleural covering on pneumothorax recurrence in BHDS patients. RESULTS: This retrospective study enrolled a total of 81 pneumothorax patients with the diagnosis of BHDS who underwent 90 covering surgeries from January 2010 to August 2017 at Tamagawa Hospital. During the first half of the study period, a lower pleural covering (LPC) which covered the affected area with ORC mesh was mainly used to treat 38 pneumothoraces. During the second half of the study period, TPC was primarily performed for 52 pneumothoraces. All the thoracoscopic surgeries were successfully performed without serious complications (≥ Clavien-Dindo grade III). The median follow-up periods after LPC/TPC were 66/34 months, respectively. Pneumothorax recurrence rates after LPC at 2.5/5/7.5 years postoperatively were 5.4/12/42%, respectively; none of the patients who had underwent TPC developed postoperative pneumothorax recurrence (P = 0.032). CONCLUSIONS: TPC might be an effective option for surgical treatment of intractable pneumothorax in patients with BHDS.

Two Kinds of Cystic Lung Lesions with Pulmonary Lymphangioleiomyomatosis in a Male.

A 34-year-old male with frequent recurrence of right pneumothorax was admitted to our hospital. He was a current smoker and outwardly male without genital aplasia. He was diagnosed as tuberous sclerosis complex (TSC) at 2 year-old and underwent transcatheter arterial embolization for right renal hemorrhage due to renal tumor 2 years ago. Chest Computed Tomography showed that he had multiple tiny round cystic lesions with thin wall in both lungs. The recurrent pneumothorax was expected to be associated with TSC-Lymphangioleiomyomatosis (LAM). Video-assisted thoracic surgery was successfully performed. The operative and histological findings revealed that the bullae were classified into two groups; emphysematous bullae and bullae due to LAM. His postoperative course was uneventful. TSC-LAM is extremely rare, but in some cases the clinical recognition might be escaped due to subtle findings of bullae in early LAM, resulting in diagnosis as spontaneous pneumothorax.

Left-Sided Catamenial Pneumothorax with Thoracic Endometriosis and Bullae in the Alveolar Wall.

Catamenial pneumothorax (CP) is generally caused by intraperitoneal air leaking from the uterus into the thoracic cavity via a defect in the endometrial tissue of the diaphragm and is usually detected in the right thorax. We report a case of left-sided CP caused by endometriosis in the visceral pleura and with no abnormal findings in the diaphragm. A 33-year-old female patient presented at the end of a course of low-dose contraceptive pills for pelvic endometriosis, with spontaneous pneumothorax in the left chest. Chest CT revealed a bulla in the left upper lung lobe. The patient underwent partial resection of the lung. Immunohistochemistry confirmed the presence of endometrial stromal tissue in the visceral pleura and confirmed this as the cause of pneumothorax since there were no observable abnormalities in the diaphragm. This case suggests that immunohistochemical examination of patients with spontaneous pneumothorax can detect alternative endometrial lesions.

A Total Pleural Covering for Lymphangioleiomyomatosis Prevents Pneumothorax Recurrence.

BACKGROUND: Spontaneous pneumothorax is a major and frequently recurrent complication of lymphangioleiomyomatosis (LAM). Despite the customary use of pleurodesis to manage pnenumothorax, the recurrence rate remains high, and accompanying pleural adhesions cause serious bleeding during subsequent lung transplantation. Therefore, we have developed a technique of total pleural covering (TPC) for LAM to wrap the entire visceral pleura with sheets of oxidized regenerated cellulose (ORC) mesh, thereby reinforcing the affected visceral pleura and preventing recurrence. METHODS: Since January 2003, TPC has been applied during video-assisted thoracoscopic surgery for the treatment of LAM. The medical records of LAM patients who had TPC since that time and until August 2014 are reviewed. RESULTS: TPC was performed in 43 LAM patients (54 hemithoraces), 11 of whom required TPC bilaterally. Pneumothorax recurred in 14 hemithoraces (25.9%) from 11 patients (25.6%) after TPC. Kaplan-Meier estimates of recurrence-free hemithorax were 80.8% at 2.5 years, 71.7% at 5 years, 71.7% at 7.5 years, and 61.4% at 9 years. The recurrence-free probability was significantly better when 10 or more sheets of ORC mesh were utilized for TPC (P = 0.0018). TPC significantly reduced the frequency of pneumothorax: 0.544 ± 0.606 episode/month (mean ± SD) before TPC vs. 0.008 ± 0.019 after TPC (P<0.0001). Grade IIIa postoperative complications were found in 13 TPC surgeries (24.1%). CONCLUSIONS: TPC successfully prevented the recurrence of pneumothorax in LAM, was minimally invasive and rarely caused restrictive ventilatory impairment.

[A SURGICAL CASE OF MYCOBACTERIUM KANSASII LUNG DISEASE MIMICKING PRIMARY LUNG CANCER].

We report a rare surgical case of a solitary pulmonary nodule due to Mycobacterium kansasii. A 59-year-old man was admitted to our hospital for examination of an abnormal shadow in the left upper lobe incidentally found on a chest radiogram. Computed tomography of the chest showed that the nodule was located in the left segment 1+2 and was irregularly shaped with a diameter of 35 mm. Thoracic fluorine-18 fluoro-deoxy-glucose positron emission tomography showed a high metabolic pulmonary lesion, with a maximum standardized uptake value of 5.1, consistent with findings for lung cancer. A bronchoscopy was performed to establish the diagnosis of lung cancer; however, it failed to show malignant cells. Because we could not confirm the diagnosis by bronchoscopic examination, video-assisted thoracoscopic surgery was performed. The intraoperative rapid diagnosis of the nodule was epithelioid cell granuloma. Smear test of the resected specimen was positive for acid-fast bacilli, and a culture was also positive for mycobacteria, which were identified as Mycobacterium kansasii. Antibiotic treatment for M. kansasii infection was administered for a year after the surgical resection. Few cases of Mycobacterium kansasii infection present with solitary pulmonary nodules.

[Bronchial hamartoma in subsegmental bronchus; report of a case].

We report a rare surgical case of a bronchial hamartoma in subsegmental bronchus. A 70-year-old man was incidentally pointed out an abnormal chest shadow without any complaints. Chest computed tomography revealed a round nodule with diameter of 15 mm in the right upper lobe. The bronchoscopic examination revealed complete obstruction of right B2a by the tumor. Right S2 segmentectomy was done to make a definite diagnosis and to prevent possible obstructive pneumonia. Histopathological examination revealed that the tumor was a benign cartilage bronchial hamartoma.

[Synchronous multiple primary lung and colon cancers].

We report a rare surgical case of synchronous multiple primary lung cancers with synchronous multiple colon cancers. A 74-year-old woman was incidentally pointed out abnormal chest shadows. Chest computed tomography revealed 2 nodules in the right upper and middle lobe. Transbronchilal lung biopsy (TBLB) was done, and the tumor in the middle lobe was diagnosed as adenocarcinoma. In addition, positron emission tomography pointed out colon cancer. Colon fiber revealed multiple colon polyps and colon cancers. Immunostaining with thyroid transcription factor (TTF)-1 and Napsin-A for TBLB specimen was done to distinguish their association. With the diagnosis as primary lung cancer, we performed right upper and middle lobectomy with lymph node dissection. These tumors were pathologically diagnosed as synchronous multiple primary lung cancers with adenocarcinoma and squamous cell carcinoma. Several months later, colon regions were resected through colonoscopic endometric mucosal resection and left hemicolectomy.

MicroRNA-224 negatively regulates p21 expression during late neoplastic progression in inflammatory bowel disease.

BACKGROUND: The development of colon cancer represents a major complication in patients with inflammatory bowel disease (IBD). The importance of microRNAs (miRs) in carcinogenesis is becoming clearer because miRs have been implicated in the regulation of cancer-related cellular processes to include apoptosis, differentiation, cell cycle progression, and immune function. In the current study, we sought to identify miR dysregulation specific to progression along the normal-inflammation-cancer axis in colonic specimens from patients with IBD. METHODS: MiR microarrays and quantitative reverse transcription PCR were used to detect and confirm dysregulated miRs. Receiver operating characteristic curve analysis was applied to evaluate the potential use of miR-224 as a neoplastic disease marker in IBD. For miR-224 target messenger RNA (mRNA) identification, mRNA microarrays were employed in combination with bioinformatic analyses, Western blotting, and luciferase activity measurements. RESULTS: We identified 30 miRs that were differentially expressed between chronically inflamed mucosae and cancers arising from IBD tissues. MiR-224 levels increased successively at each stage of IBD progression and accurately discriminated cancers from normal or chronically inflamed IBD tissues. Moreover, mRNA arrays combined with bioinformatic analyses suggested the participation of miR-224 in cell cycle regulation. Subsequently, cell cycle experiments indicated that miR-224 regulates the G1-S checkpoint. Finally, in silico prediction analyses, confirmed by Western blotting and luciferase assays, identified p21 as a specific direct mRNA target of miR-224. CONCLUSIONS: These findings reveal miR dysregulation specific to IBD-associated colorectal carcinoma. MiR-224 is overexpressed in IBD cancers and targets p21, a key cell cycle regulator. Moreover, these results establish the participation of miR-224 in IBD carcinogenesis.

Biopsy with thermally-responsive untethered microtools.

Thermally activated, untethered microgrippers can reach narrow conduits in the body and be used to excise tissue for diagnostic analyses. As depicted in the figure, the feasibility of an in vivo biopsy of the porcine bile duct using untethered microgrippers is demonstrated.

Silencing of miR-370 in human cholangiocarcinoma by allelic loss and interleukin-6 induced maternal to paternal epigenotype switch.

Cholangiocarcinoma (CCA) is a highly lethal malignant tumor arising from the biliary tract epithelium. Interleukin-6 (IL-6) is a major mediator of inflammation and contributor to carcinogenesis within the biliary tree. Previous studies suggested that enforced IL-6 contributes to cholangiocarcinogenesis through hypermethylation of several genes implicated in CCA. However, the precise mechanisms of IL-6 effects in CCA remain unclear. We now demonstrate that microRNA (miR)-370 is underexpressed in a large cohort of human CCA vs. normal liver tissues. In addition, we show that IL-6 induces a time-dependent silencing of miR-370. In addition, demethylation of CCA cells results in upregulation of miR-370. Furthermore, we demonstrate that miR-370 is imprinted, and that the Intergenic Differentially Methylated Region (IG-DMR) responsible for imprinting regulation of this genomic locus is hypermethylated in response to IL-6 treatment. In addition, the IG-DMR is hypermethylated in human CCA specimens compared to normal matched controls, in the same location as the IL-6 induced hypermethylation. Finally, miR-370 was found to regulate WNT10B in luciferase as well as western blotting experiments. Our data indicate that the paternal allele of miR-370 is normally silenced through genomic imprinting and that the overexpression of IL-6 in CCA effectively suppresses the expression of miR-370 from the maternal allele, lending support to the theory that miR-370 silencing in human CCA follows a classic two-hit mechanism.

Coordinated effects of microRNA-494 induce G2/M arrest in human cholangiocarcinoma.

MicroRNA (miRs) have emerged as salient regulators in cancer homeostasis and, recently, as putative therapeutics. Cholangiocarcinomas (CCA) are aggressive cancers with survival usually measured in months. mRNA arrays followed by pathway analysis revealed that miR-494 is a major modulator of the cell cycle progression from gap 2 (G2) to mitosis (M). We performed fluorescence activated cell sorting (FACS) as well as differential interference contrast (DIC) microscopy, and confirmed that miR-494 induces a significant arrest in G2/M in CCA cells. Furthermore, we verified that miR-494 modulates the protein level of six genes involved in the G2/M transition: Polo-like Kinase 1 (PLK1), pituitary tumor-transforming gene 1 (PTTG1), Cyclin B1 (CCNB1), cell-division cycle 2 (CDC2), cell-division cycle 20 (CDC20) and topoisomerase II α (TOP2A). Next, we identified direct binding of miR-494 to the open reading frame (ORF) and downregulation of PTTG1 and TOP2A. In summary, our findings suggest that miR-494 has a global regulatory role in cell cycle progression, exerted by concerted effects on multiple proteins involved in gap 1 (G1) to synthesis (S), as described previously, as well as G2 to M progression. Therefore, it appears that the simultaneous effects of a single miR species on multiple targets along the same canonical pathway is advantageous for the usage of miRs as therapeutics. In addition, our data suggest that miRs act within a narrow range. miR expression above the upper threshold does not appear to induce further effects, which is reassuring in terms of off-target effects of miR surrounding noncancerous tissue.

MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer.

BACKGROUND: A thorough understanding of gastric cancer at the molecular level is urgently needed. One prominent oncogenic microRNA, miR-21, was previously reported to be upregulated in gastric cancer. METHODS: We performed an unbiased search for downstream messenger RNA targets of miR-21, based on miR-21 dysregulation, by using human tissue specimens and the MKN28 human gastric carcinoma cell line. Molecular techniques include microRNA microarrays, cDNA microarrays, qRT-PCR for miR and mRNA expression, transfection of MKN28 with miR-21 inhibitor or Serpini1 followed by Western blotting, cell cycle analysis by flow cytometry and luciferase reporter assay. RESULTS: This search identified Serpini1 as a putative miR-21 target. Luciferase assays demonstrated direct interaction between miR-21 and Serpini1 3'UTR. miR-21 and Serpini1 expression levels were inversely correlated in a subgroup of gastric cancers, suggesting a regulatory mechanism that included both of these molecules. Furthermore, Serpini1 induced growth retardation of MKN28 and induced vigorous G1/S arrest suggesting its potential tumour-suppressive function in the stomach. CONCLUSION: Taken together, these data suggest that in a subgroup of gastric cancers, miR-21 is upregulated, inducing downregulation of Serpini1, which in turn releases the G1-S transition checkpoint, with the end result being increased tumour growth.

MicroRNA down-regulated in human cholangiocarcinoma control cell cycle through multiple targets involved in the G1/S checkpoint.

UNLABELLED: MicroRNAs (miRs) recently emerged as prominent regulators of cancer processes. In the current study we aimed at elucidating regulatory pathways and mechanisms through which miR-494, one of the miR species found to be down-regulated in cholangiocarcinoma (CCA), participates in cancer homeostasis. miR-494 was identified as down-regulated in CCA based on miR arrays. Its expression was verified with quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). To enforce miR expression, we employed both transfection methods, as well as a retroviral construct to stably overexpress miR-494. Up-regulation of miR-494 in cancer cells decreased growth, consistent with a functional role. mRNA arrays of cells treated with miR-494, followed by pathway analysis, suggested that miR-494 impacts cell cycle regulation. Cell cycle analyses demonstrated that miR-494 induces a significant G1/S checkpoint reinforcement. Further analyses demonstrated that miR-494 down-regulates multiple molecules involved in this transition checkpoint. Luciferase reporter assays demonstrated a direct interaction between miR-494 and the 3'-untranslated region of cyclin-dependent kinase 6 (CDK6). Last, xenograft experiments demonstrated that miR-494 induces a significant cancer growth retardation in vivo. CONCLUSION: Our findings demonstrate that miR-494 is down-regulated in CCA and that its up-regulation induces cancer cell growth retardation through multiple targets involved in the G1-S transition. These findings support the paradigm that miRs are salient cellular signaling pathway modulators, and thus represent attractive therapeutic targets. miR-494 emerges as an important regulator of CCA growth and its further study may lead to the development of novel therapeutics.